Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory

Context: We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women. Objective: Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone. Design, Setting, Participants, and Intervention: In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71 ± 0.6 kg/m²; age, 57.61 ± 1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle. Main Outcome Measures: Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured. Results: Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44 ± 0.63 yr), i.e. insulin administration did not affect food intake (P > 0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (P < 0.05). Conclusions: Low estrogen levels as present in postmenopausal women do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.